Nothing is Impossible

BPJ_112_10.c1.inddRecent work in molecular bioelectricity has demonstrated the ability to radically alter animals’ morphology despite a normal genomic sequence. Cells make decisions and cooperate towards complex anatomical goal states using bioelectric gradients that are only detectable in the living state and invisible to the mainstream protein or mRNA profiling approaches. The study of these non-neural bioelectrical networks have allowed us to create living “impossible objects” in the highly regenerative planarian flatworm system. For example, flatworms can be made permanently two-headed by a transient change of their bioelectrical circuit. A brief shift of their bioelectric network to a new attractor state permanently alters their pattern memory so that in the future, they will regenerate as two-headed forms out of middle fragments cut in plain water, despite their wild-type genomic sequence.  M. C. Escher was an artist with a keen appreciation of “impossible” or “undecidable” objects, drawing many two-dimensional forms (such as ever-descending staircases) that cannot exist in our three-dimensional world.

We drew inspiration for our image on the cover of the May 23 issue of Biophysical Journal from Escher’s visions, as the worms we report in our paper are in a sense “impossible objects,” whose target morphology does not match their current anatomy. They are also “undecidable objects” because each worm stochastically decides to be one or two-headed upon amputation, persisting in an undecided state. The image is specifically based on the M. C. Escher woodcut Another World II, a.k.a. Other World II, which masterfully depicts paradoxical views of an alien landscape, revealing different aspects of reality but not matching our expectations based on the perspective we take looking through each of the windows in the structure.

ImageThis image is a perfect complement to our work on the physiological determinants of patterning. These experiments revealed a new perspective on the control of biological anatomy, which exhibit rules and properties quite different from what is seen when the same object is viewed through the portal of genetic networks or biochemical gradients. To adapt the original woodcut for this image, the color was changed to the blue/red pseudocoloring used to image voltage gradients in the planaria, and the bird-like creature Escher used in the original has been changed to one- or two-headed planaria.

Interestingly, Escher was well aware of the remarkable properties of planaria, as shown  in his 1959 lithograph Planaria (Flatworms). However, the study of bioelectric regulation of growth and form applies well beyond planaria.  It is relevant to the detection and repair of birth defects (especially of the face, brain, and left-right axis), the induction of regeneration of limbs, and detection or reprogramming of cancer, as well as synthetic bioengineering. Much like neural networks in the brain, somatic bioelectric networks store pattern memories and process information that guide development, regeneration, and cancer suppression. Beyond biomedical applications in regenerative medicine and bioengineering, the study of bioelectric communication within tissues in vivo is a branch of the emerging field of primitive cognition.

Evolution takes advantage of biophysical processes to drive computation and decision-making in the brain and body; learning to manipulate this process may allow us to achieve currently impossible biological objects, with structure and function far beyond those we can envision today.

The cover image was created by Jeremy Guay, of Peregrine Creative.

– Fallon Durant, Junji Morokuma, Christopher Fields, Katherine Williams, Dany Adams, Michael Levin

Biophysicists Finding Balance: Mother’s Day 2017

May 14 is Mother’s Day in the US. In honor of the occasion, we spoke with Biophysical Society members Eva-Maria Collins, UC San Diego, and Sarah Veatch, University of Michigan, about what it is like to be a biophysicist and a parent, and how the two roles impact each other.

Eva-Maria Collins


Collins speaking at the 2017 Biophysical Society Annual Meeting with daughter in tow.

How many children do you have? What are their ages?

We have a 3 year old boy and a 10 months old daughter.

At what stage of your career did you have your children? 

I am currently an Assistant Professor at UCSD and had both kids here while on tenure track.

Has your career been influenced or changed by your role as a parent? How?

Without a doubt! When pregnant with our son I started worrying about handling chemicals while doing experiments in the lab. Realizing that we know way too little about how different chemicals in our environment affect brain development, we started a new research direction in my group developing planarians for high-throughput developmental neurotoxicology screening. In addition, my priorities have shifted. While I still love my work, my kids always come first.

How has your career been influenced by your own parents?

My career has definitely been influenced by my parents in the sense that they were always supportive and encouraged me to follow my dreams. Although my mother was a housewife (I am one of 6 children) and my father worked in administration, they both supported me at every step along the way – and still do!

What has been the most challenging aspect of being a biophysicist and a parent?

Time balance between work and family life. Feeling guilty a lot for not spending enough quality time with either. I am sure a lot of parents feel this way and being in academia, we actually have it very good in the sense that our job is relatively flexible and allows us to take time off to take care of our family when we need it. I also was able to bring both kids to work with me the first 6-7 months of their lives. This was wonderful, because I could experience their every milestones and share videos of it with my husband who works in industry and did not have that opportunity.

Have there been any benefits to being both a mother and a scientist?

Yes! I have gotten more effective with my time, I had to learn to say NO more often, to prioritize my projects, and to let things go that are less important and know it’s OK to do so. I also think that I have become a better mentor for my students as a mother.

Would you encourage your children to be scientists?

I don’t really care what they’ll become as long as they are passionate about what they will be doing and help make this world a better place. I hope to follow in my parents’ footsteps in this respect to make sure we’re always there to support them while simultaneously giving them the freedom to shape their own lives.

How would your children describe your work?

The youngest doesn’t talk yet. Our 3 year old loves coming to work with me because he can ride an elevator and see some fork lifts or other big trucks. I don’t think he cares too much about what I actually do yet.

Any advice for other mothers or prospective mothers pursuing science careers?

Don’t let anyone tell you that you have to make a choice between having a family and having a career. One can do both and one does not have to wait until after tenure. It’s not easy to juggle both, but with a supportive partner and the right mindset (not everything has to be perfect all the time!), being a parent and a scientist may actually bring out the best in you for both worlds.

photoSarah Veatch

How many children do you have? What are their ages?

2 boys, they are 2 and 5.

At what stage of your career did you have your children? 

As an assistant professor — but a note that my partner carried and breast-fed both kids, so I’ve had it easier than many other mom scientists.

Has your career been influenced or changed by your role as a parent? How?

I don’t think so.  It is common in my university for Assistant Professors to have small children.  I think the biggest difference for me before and after kids is my shifting of priorities.  Family is now right up there with my work in terms of importance and time commitment, and before kids I could get away with prioritizing work over just about anything else. I think that the biggest changes are that I sleep less now and have less ‘down’ time with friends and my partner.

How has your career been influenced by your own parents?

A lot.  My father, who died when I was young, was a scientist.  My step-father is a scientist, and my mom is a medical doctor who is also very invested in science and the scientific method. Being a scientist is very valued in my immediate family, and I think that this made some of the sacrifices made to take this career path were easier to justify to them.

What has been the most challenging aspect of being a biophysicist and a parent?

I think that my biggest challenge both before and after kids is having only finite time and finite mental energy to accomplish all that needs to be done.  Including kids in the equation just makes my time doing science even more valuable and appreciated.

Have there been any benefits to being both a mother and a scientist?

My kids (and probably all kids) are amazing – they help me to see the world from different perspectives, they pick up on everything, and they demand my attention in a way that requires that I let go the problems of the day (being late on that review assignment, debugging code or troubleshooting that experiment, etc.).

Would you encourage your children to be scientists?

I want to foster critical thinking in my kids, and I think this naturally lends itself to scientific thinking.  I think that being a scientist is the best job in the world (for me at least), and I hope that they can be fortunate enough to find a career that brings them as much joy as I experience.

How would your children describe your work?

My 5 year old son said (roughly) that “momma learns by looking at cells with a microscope”

Any advice for other mothers or prospective mothers pursuing science careers?

I am not sure that the advice differs from people pursuing science careers – Find what you love, work hard to stand out, and tell people about your successes.  There are never enough hours in the day to do everything even without kids, so you always have to choose to focus on what matters most at the moment.

A Shape Shifting Surface Layer

BPJ_112_9.c1.inddSurface layers (S-layers) are shells of protein that surround many microbes. Most S-layers are made of one or two proteins that self-assemble into a very thin protein crystal. Crystalline S-layers serve many functions in prokaryotes, including protection and shape determination. In some cases, crystalline S-layers enable pathogenic bacteria to infect humans, either by making the bacterium sticky, or by helping it avoid detection by our immune system. Surprisingly, the S-layer protein from the bacterium Caulobacter crescentus is not always crystalline, and can form two different structures on the surface of the cell.

Caulobacter crescentus is a crescent-shaped bacterium that can be found in many freshwater environments. The cover image for the May 9th issue of the Biophysical Journal is an artistic rendering of Caulobacter crescentus cells swimming in their natural habitat. The left side of the image depicts the surface of a single Caulobacter cell. Caulobacter’s S-layer protein can assume two forms, shown in green and blue. The green form is crystallized S-layer protein, which makes a hexagonal pattern on the surface of the cell. The blue form is an amorphous aggregate of the S-layer protein. That is, the protein is jumbled up and can’t make a repeating pattern.

Most previous work on S-layers has suggested that S-layers are crystalline out of necessity. However, our work indicates that in at least one case, this is not true. This inspired the creation of this cover image, which shows a surface layer that consists of two structural states: crystalline and amorphous. With this study and image, we hope to inspire further investigation into the structural flexibility, rather than the crystallinity, of S-layers.

Artist: Greg Stewart/SLAC

– Fatemeh Jabbarpour, Paul Bargar, John Nomellini, Po-Nan Li, Thomas Lane, Thomas Weiss, John Smit, Lucy Shapiro, Soichi Wakatsuki, Jonathan Herrmann

Lipid vesicles on the beat

BPJ_112_8.c1.inddThe cell plasma membrane serves not only as a protective barrier but as the first responder to a changing environment. One environmental challenge these cells face is osmotic stress — where an imbalance of, for instance, ions or sugars, across the plasma membrane exerts osmotic pressure on the membrane. In order to deal with osmotic stress, mammalian cells have evolved complex protein machineries. But how do simpler cells respond to an osmotic onslaught? We answer this question by studying cell-sized lipid vesicles in osmotic stress. Surprisingly, they display a pulsatile behavior, swelling, bursting, and resealing their membrane cycle after cycle!

The cover image for the April 25 issue of the Biophysical Journal is an artistic rendering of the pulsatile dynamics of cell-sized vesicles in osmotic stress. The red fluorescent vesicles represent experimental observations of giant unilamellar vesicles at three stages of the osmotic swell-burst cycle: relaxed (left), swollen (middle), and ruptured with a burst of fluorescent green sucrose (right). On the piece of paper, the vesicles are projected onto corresponding schematics depicting the different stages of the cycle. The leading processes driving the pulsatile behavior, osmotic pressure, surface tension, and leak-out velocity, are defined in mathematical terms. On the top-right of the paper, is one of the key equations we proposed, representing the dynamics of a pore in the membrane taking into account stochastic pore nucleation induced by thermal fluctuations.

This cover was inspired by the combined experimental and theoretical approaches we embraced in this study. It shows how, from experimental observations (the red vesicles), a conceptual model can be built and formalized into mathematical terms (the schematics) to understand the underlying mechanisms of pulsatile vesicles. By mirroring “realistic” vesicles with “hand-drawn” schematics, the cover illustrates how the complexity of a real world process can be reduced to its essential features through modeling. This fundamental scientific approach allows us to build a testable hypothesis to unravel the biophysical principles behind experimental observations.

Through our study and this cover, we highlight how combining experimental and theoretical approaches can be a powerful way to tackle complex challenges, especially for fundamental problems at the frontier between biology, chemistry, and physics.

—Morgan Chabanon, James CS Ho, Bo Liedberg, Atul Parikh, Padmini Rangamani

How to Prepare for a Non-Bench Career


Professor Molly Cule is delighted to receive comments on her answers and (anonymized) questions at, or visit her on the BPS Blog.

There is an increasing interest for science PhD students to pursue an “alternate” career beyond the traditional bench research followed by a tenure-track faculty position. The options include marketing, sales, intellectual property, policy, and writing, among others. This article highlights four important steps you can take to prepare for any of these non-bench careers.

  • Do your research: Do not go into another non-bench career just for the sake of it. The career sections of most societies, as well as top journals like Science and Nature have a treasure trove of information on various alternative careers. Reach out to alumni from your school or your lab, as well as to friends and family members, or use social media (Twitter/LinkedIN) to directly speak with people who have made the transition.
  • Along the same lines, make a list of your transferrable skills. These skills could have been built up either as part of your graduate research (e.g., data mining and analysis), or at home or through community work (e.g., did you demonstrate leadership skills through some sort of volunteer work?).  Then note how they align with the careers you are considering.
  • Work on your communication skills: Most non-bench careers involve effective communication, whether it is written or verbal. Two particular skills that will be useful to master include (a) the ”elevator pitch” — a quick summary of who you are and/or what you do and why it’s valuable, and (b) communicating technical information to a lay audience.
  • Gain experience outside of your work: It can be difficult to break into a new industry without prior experience. However, it is possible to gain experience in other ways. If you are interested in science writing, think of maintaining an active blog, or contribute to your school or society newsletters; see if you can volunteer at your institute’s technology commercialization office if you are interested in patent law. Employers also tend to look favorably upon those who have demonstrated a willingness to broaden their horizons beyond bench research.
  • Network: It’s gotten to be a cliché now, but the value of the mantra ”Network, network, network” cannot be overstated. Apart from helping you land that next job, networking will help all of the above — researching alternate careers, communicating, and broadening your horizons!

Modeling Unravels the Upper Limit of Mitotic Spindle Size

BPJ_112_7.c1.inddWhen talking about organelle size, most people believe the bigger the cell, the larger the organelle should be. In fact, this is not true, at least for mitotic spindles. Recent studies showed that the mitotic spindle size scales with the cell size in small cells, but approaches an upper limit in large cells. However, how the spindle size is sensed and regulated still eludes scientists.

The cover image for the April 11 issue of the Biophysical Journal shows a configuration sampled by a three-dimensional computational simulation guided by a general model for mitotic spindles. The model explicitly shows microtubules (colorful rods), centrosomes (green sphere), and chromosomes (pink bulks). Microtubules can be nucleated from the centrosomes, grow outward, and show the dynamic instability. When microtubules encounter the cortex or chromosome arms, they can generate pushing forces (red rods) due to the polymerization of microtubules. Various molecular motors on cortex and chromosomes, including dyneins (yellow dots) and kinesins (green dots), can bind to microtubules and generate pushing forces (green rods) or pulling forces (blue rods). Therefore, the centrosomes and chromosomes can move under these forces. In this way, the mitotic spindle can be self-assembled to form a bipolar structure with certain size, positioned to the cell center, and orientated to the long axis. Meanwhile, the chromosomes can be attached correctly and aligned on the equatorial plate.

This computational model is very useful for studying the size regulation of mitotic spindles. The spindle size is usually defined as the pole-to-pole distance, so that the problem of spindle size regulation is dependent on the positioning of two poles. The position of each pole is determined by the mechanical equilibrium between the cortical force and the chromosome force on the spindle pole.  For each pole, the chromosomes and the cortex are geometrically asymmetric. In small cells, the geometric asymmetry is small and the pole is nearly positioned to at the center of each half cell so that the spindle size scales with the cell size. However, in large cells, because few microtubules can reach the cell boundary, the geometric asymmetry is large and the spindle size is only determined by the chromosomes; that is, the spindle size approaches the upper limit. Therefore, this work revealed a novel and essential physical mechanism of the spindle size regulation.

There are certainly many other factors that influence spindle size but only quantitatively; they cannot explain the existence of the size limit of spindles.

This computational model provides a very powerful and robust tool. It can be combined with existing biochemical techniques to explore many important and interesting phenomena, including the positioning and orientation of mitotic spindles, the spontaneous oscillation of chromosomes, the mechanical response of spindles under various forces, and many other relevant questions.

– Jingchen Li and Hongyuan Jiang

Understand the Regulation of Learning and Memory Formation from a Molecular Prospective

BPJ_112_6.c1.inddWhen most people talk about calcium (Ca2+), they think about building bones and muscle contraction. In fact, calcium is also essential for learning and memory formation. Molecular basis for learning and memory formation has aroused attention since 1980s.  So what does calcium do with learning and memory formation? The calcium-modulating protein calmodulin (CaM) coordinates the activation of a family of Ca2+-regulated proteins, which are crucial for synaptic plasticity associated with learning and memory in neurons. These proteins include neurogranin (Ng) and CaM-dependent kinase II (CaMKII). In a resting cell, CaM is mostly reserved by Ng and free of Ca2+, whereas in a stimulated cell, CaM is able to bind Ca2+ and activate CaMII, which plays a pivotal role in learning and memory formation for both long-term potentiation and mechanisms for the modulation of synaptic efficacy.

The cover image for the March 28 issue of the Biophysical Journal shows the crystal structure of CaM-CaMKII peptide and the structure of CaM-Ng from coarse-grained molecular simulations. CaM molecules are ribbons in silver, calcium ions are represented by yellow beads, CaMKII peptide is in green surface representation, and Ng peptide is in red surface representation. One CaM-Ng peptide complex is near, where the Ng is aligned with a “pry” (pink); the other is far, indicating rich level of Ng. The images were rendered using the software Visual Molecular Dynamics developed by University of Illinois at Urbana-Champaign with the built-in Tachyon ray tracer. The illustration of a neuron in hippocampus is taken from Shelley Halpain, UC San Diego. Dendrites are green, dendritic spines red, and DNA (in cell nucleus) blue. The illustration of a human brain contains red dots to indicate active parts of the cerebral cortex.

Our computational study provides the very first detailed description at atomistic level ofhow binding of CaM with two distinct targets, Ng and CaMKII, influences the release of Ca2+ from CaM, as a molecular underpinning of CaM-dependent Ca2+ signaling in neurons. We believe this study bridges the molecular regulations in atomistic detail and the understanding of cellular process cascade of learning and memory formation.

– Pengzhi Zhang, Swarnendu Tripathi, Hoa Trinh, Margaret S. Cheung